Open AccessTargeting of RNA Polymerase II by a nuclear Legionella pneumophila Dot/Icm effector SnpL
Author(s) -
Schuelein Ralf,
Spencer Hugh,
Dagley Laura F.,
Li Peng fei,
Luo Lin,
Stow Jennifer L.,
Abraham Gilu,
Naderer Thomas,
GomezValero Laura,
Buchrieser Carmen,
Sugimoto Chihiro,
Yamagishi Junya,
Webb Andrew I.,
Pasricha Shivani,
Hartland Elizabeth L.
Publication year - 2018
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12852
Subject(s) - effector , biology , legionella pneumophila , microbiology and biotechnology , ectopic expression , transcription factor , elongation factor , transcription (linguistics) , rna polymerase ii , gene expression , gene , rna , genetics , promoter , ribosome , linguistics , philosophy , bacteria
The intracellular pathogen Legionella pneumophila influences numerous eukaryotic cellular processes through the Dot/Icm‐dependent translocation of more than 300 effector proteins into the host cell. Although many translocated effectors localise to the Legionella replicative vacuole, other effectors can affect remote intracellular sites. Following infection, a subset of effector proteins localises to the nucleus where they subvert host cell transcriptional responses to infection. Here, we identified Lpw27461 (Lpp2587), Lpg2519 as a new nuclear‐localised effector that we have termed SnpL. Upon ectopic expression or during L. pneumophila infection, SnpL showed strong nuclear localisation by immunofluorescence microscopy but was excluded from nucleoli. Using immunoprecipitation and mass spectrometry, we determined the host‐binding partner of SnpL as the eukaryotic transcription elongation factor, Suppressor of Ty5 (SUPT5H)/Spt5. SUPT5H is an evolutionarily conserved component of the DRB sensitivity‐inducing factor complex that regulates RNA Polymerase II dependent mRNA processing and transcription elongation. Protein interaction studies showed that SnpL bound to the central Kyprides, Ouzounis, Woese motif region of SUPT5H. Ectopic expression of SnpL led to massive upregulation of host gene expression and macrophage cell death. The activity of SnpL further highlights the ability of L. pneumophila to control fundamental eukaryotic processes such as transcription that, in the case of SnpL, leads to global upregulation of host gene expression.